University of Groningen
tRNA mimicking structures to control and monitor biological processes Paul, Avishek
DOI:
10.33612/diss.166342562
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Publication date: 2021
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Paul, A. (2021). tRNA mimicking structures to control and monitor biological processes. University of Groningen. https://doi.org/10.33612/diss.166342562
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Chapter 6
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Since the TMS switch is trans encoded, it can be implemented to target any gene in the bacterial genome as it was demonstrated in chapter 2. The same conclusion is true for the ssDNA switch (chapter 4). This feature of the TMS switch could propel its application toward engineering metabolic flux of bacterial community. One potential hurdle in engineering bacterial metabolic flux is to produce the desired compound without compromising cell viability. Previously, lysine riboswitch was used to regulate flux of carbon containing precursors through the citric acid (TCA) cycle1. But implementation of the cis encoded lysine riboswitch
is limited with only one input (lysine) and in some situation it may not bode well with bacterial viability as cis encoded switch implementation demands some genetic sequence alteration in the target mRNA.
Apart from targeting any gene in bacterial genome, bacteria containing TMS switch can be implemented to deliver drugs in mammalian cells2. Recently a
genetic switch was designed to lyse the bacterial cells using quorum sensing as trigger3. To advance the reported system, TMS switch could be used to control
EDFWHULRSKDJHO\VLVJHQH ij;( ZLWKOLJKWDVLQSXWVLJQDO7KHFRQFHSWWKDW was described in chapter 3 can be implemented to trigger the lysis gene expression with a specific wavelength of light and lyse the bacterial cells. In this way a therapeutic gene can be expressed in bacteria and by triggering the expression of the lysis gene in bacteria at a specific location in human body one can control the spatiotemporal release of the drug produced by the bacteria. Beside controlling release mechanism of a drug from a bacterial host, our genetic switches could also be applied to engineer the motility of bacteria so that bacteria can be channelled to a desired target. Bacterial chemotaxis has been studied extensively and is well understood at the genetic level. The ability to modulate bacterial motility with our designed TMS switch in response to an input chemical signals would provide an advanced and sophisticated tool for drug delivery. In this regard, we could hypothesize that the E. coli chemotaxis system could be reprogrammed by placing a key chemotaxis signalling protein (cheZ) under the control of our TMS switch. In the downstream event, if the switch can be controlled by a ligand which is produced or can be found in the desired target location then the bacterial host carrying the therapeutic protein can be directed toward the target location.
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References
1. Zhou, L. B. and A. P. Zeng (2015). "Exploring lysine riboswitch for metabolic flux control and improvement of L-lysine synthesis in Corynebacterium glutamicum." ACS Synth Biol 4(6): 729-734.
2. Steidler, L., et al. (2000). "Treatment of murine colitis by Lactococcus lactis secreting interleukin-10." Science 289(5483): 1352-1355.
3. Din, M. O., et al. (2016). "Synchronized cycles of bacterial lysis for in vivo delivery." Nature 536(7614): 81-85.
